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TNFR1 mediates TNF-...
TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
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- Ji, Hong (author)
- Karolinska Institute, Sweden; Nanjing Medical University, Peoples R China
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- Cao, Renhai (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Yang, Yunlong (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Zhang, Yin (author)
- Karolinska Institute, Sweden
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- Iwamoto, Hideki (author)
- Karolinska Institute, Sweden
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- Lim, Sharon (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Nakamura, Masaki (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Andersson, Patrik (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Wang, Jian (author)
- Karolinska Institute, Sweden
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- Sun, Yuping (author)
- Shandong University, Peoples R China
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- Dissing, Steen (author)
- University of Copenhagen, Denmark
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- He, Xia (author)
- Nanjing Medical University, Peoples R China
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- Yang, Xiaojuan (author)
- Karolinska Institute, Sweden
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- Cao, Yihai (author)
- Linköpings universitet,Institutionen för medicin och hälsa,Medicinska fakulteten,Karolinska Institute, Sweden; University of Leicester, England
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(creator_code:org_t)
- 2014-09-17
- 2014
- English.
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In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 5:4944
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https://www.nature.c...
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Abstract
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- Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-alpha-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(+/+) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-alpha-TNFR1 pathway.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ji, Hong
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Cao, Renhai
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Yang, Yunlong
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Zhang, Yin
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Iwamoto, Hideki
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Lim, Sharon
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show more...
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Nakamura, Masaki
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Andersson, Patri ...
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Wang, Jian
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Sun, Yuping
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Dissing, Steen
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He, Xia
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Yang, Xiaojuan
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Cao, Yihai
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
- Articles in the publication
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Nature Communica ...
- By the university
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Linköping University
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Karolinska Institutet